1. Field
The present disclosure relates to antibodies specifically binding to angiopoietin-2, fragments thereof, and use of the antibodies.
2. Description of the Related Art
Angiogenesis is a process involving the growth of new blood vessels from pre-existing vessels. Angiogenesis plays a vital role in the formation of organs, normal biological growth, and wound healing. In addition, abnormal angiogenesis is known to be an important contributor to diseases such as development and metastasis of tumors, age-related macular degeneration, diabetic retinopathy, psoriasis, rheumatoid arthritis, and chronic inflammation.
Since development and metastasis of tumors depend on angiogenesis, it has been suggested that anti-angiogenesis drugs would be novel anti-cancer drugs. Therefore research into the mechanism of angiogenesis has been conducted to develop new anti-cancer drugs. One of the target proteins is angiopoietin. Angiopoietin, an angiogenesis factor, is known to participate in blood vessel development and angiogenesis after birth. Examples of identified angiopoietins include angiopoietin-1, angiopoietin-2, angiopoietin-3, and angiopoietin-4.
Angiopoietins, in concert with vascular endothelial growth factor (VEGF), are a family of growth factors that modulate tumor angiogenesis mediated through the Tie2 receptor, which is highly expressed in growing blood endothelial cells. Angiopoietin-2 (Ang-2) binds to Tie2. Among the various angiopoietins, Angiopoietin-2 (Ang-2) when alone, regresses blood vessels. However, the blood vessel regression causes hypoxia within the cancer tissue, which is an environment in which angiogenesis is possible. Under such condition, expression of VEGF is increased, and new blood vessels are formed.
Preclinical and clinical trials are being conducted on various kinds of the currently available angiogenesis inhibiting agents. Although a few antagonists of the biological activity of angiopoietin-2 are known, such as an antibody specifically binding Ang-2 which has been shown to reduce tumor angiogenesis, and growth in some tumor models, there is a need for additional angiopoietin-2 antagonists displaying anti-cancer and/or anti-angiogenesis effects.